Aim: Tebentafusp, used for advanced uveal melanoma, involves intra-patient dose escalation to decrease the likelihood of cytokine release syndrome (CRS). Inpatient admission is recommended for the dose escalation for CRS monitoring and to provide appropriate supportive treatment. This audit aims to describe the incidence and potential risk factors for symptomatic CRS (Grade 2 or above) in a real-world setting.
Methods: A retrospective audit was conducted of tebentafusp use at two hospitals between 01/07/2021 and 15/06/2024 by a single prescriber. Data collected included burden of liver disease, baseline blood pressure, and presence and Grade of CRS. Results were compared to the pivotal Phase III trial data.
Results: Fifteen patients received therapy, 47% (n=7) experienced CRS Grade 2 or above (Grade 2 n=5, 33%; Grade 3 n=2, 13%) versus 77% of patients in the trial setting. Five out of the 7 patients had at least 50% of the liver involved with metastatic disease (4 had >75%, 1 had 50%, and 2 had <25%), compared to the patients who did not have CRS Grade 2 or above, where only 2 out of 8 had at least 50% of the liver involved with metastatic disease (2 had 50%, 6 had <25%). Four out of the 7 (57%) patients in the symptomatic CRS group had lactate dehydrogenase (LDH) 3x the upper limit of normal (ULN) compared to none in the group that did not experience symptomatic CRS. In this case series, all symptomatic CRS occurred at the first dose of tebentafusp, with 2 patients discontinuing treatment post-first dose due to rapid progression.
Conclusion: Burden of liver disease and LDH 3xULN were associated with an increased risk of symptomatic CRS. Future research should explore a larger real-world patient cohort to identify high-risk patients, removing the requirement for inpatient admission during dose escalation for low-risk patients.